Synergistic effect of GRA7 and profilin proteins in vaccination against chronic Toxoplasma gondii infection

ARCÓN, NADIA; M PICCHIO; FENOY I; MORETTA R; A SOTO; M PERRONE SIBILIA; SANCHEZ VR; PRATO, CA; V TRIBULATTI; A GOLDMAN; MARTIN V

VACCINE

ELSEVIER SCI LTD

Lugar: Amsterdam; Año: 2021

0264-410X

Toxoplasma gondii infection is a zoonotic disease with worldwide prevalence in humans and warm-blooded animal populations. In livestock Toxoplasma gondii is the causal agent of significant economic losses since it can cause abortions in goats and sheep. It is estimated that one third of the world population is infected. Although there are effective therapies for acute infection, these are sometimes poorly tolerated, teratogenic, and have a long administration time. Taking into account the deficiencies that exist related to the prevention and treatment of toxoplasmosis, the development of a safe and effective vaccine would be extremely valuable in fighting against this infection. In the present work, we characterize for the first time the adjuvant and antigen potential of a recombinant profilin protein (rTgPF), in a vaccine formulation alone or in combination with the well-known GRA7 antigen candidate in a murine toxoplasmosis model. Since TgPF acts as a ligand for both TLR11 and 12 inducing innate immune responses that promote type 1 adaptive responses, we first study the capacity of the mix rGRA7+rTgPF to initiate an immune response by evaluating dendritic cell activation. Both rTgPF and rGRA7 induces activation of mouse BMDCs more efficiently than the single proteins, evidenced by the increase in the expression of CD80 and CD86 co-stimulatory proteins and the secretion of IL-6, IL-10 and IL-12 cytokines after in vitro stimulation. The sum effects of rGRA7 and rTgPF on BMDCs maturation led us to assay them in a vaccination protocol. BALB/c mice vaccinated with this mix elicited a Th1-biased immunity via the induction of lymphocyte proliferation, activation of CD4+T cells and increased IFN-γ production that resulted in enhanced protection against chronic Toxoplama gondii infection. We postulate rTgPF as a potential adjuvant in a protein vaccine formulation since it does not induce cellular and humoral immunity by itself but enhances the effect of rGRA7 when used together